Genome-wide association study in 2,053 unrelated ankylosing spondylitis cases among people of European descent (69 Australian, 1129 British and 983 North American) and 5,140 ethnically matched controls derived from British Birth Cohort genotyped by WTCC (1436) and Illumina iControlDB database (4149). HapMAP CEU (North & Western European), YRI (Nigeria), JPT (Japan), CHB(Chinese) samples (262) were added to the control to use for quality control. Genotyping was performed with Illumina HumHap370 genotyping chips and 288,662 SNPs were available for analysis. Imputation analyses were carried out with MACH, using phased data from CEU invidividuals from release 22 of HapMap project. Replication was performed by IPLEX technology or by KASPar technology in an independent cohort of 898 British ankylosing spondylitis cases and 1,518 unselected British controls.This study reports four novel genetic loci associated with ankylosing spondylitis risk and identifies a major role for the interleukin (IL)-23 and IL-1 cytokine pathways in disease susceptibility.
Samples Exclusion: Related individuals (410 samples) containing 62 cases and 135 of the HapMap quality-control samples that consisted of related members of family trios.
|Region||Location||Gene(s)||Marker||Allele||MAF||P Value||Odds Ratio|
|1p31.3||chr1:67128876-67302310||IL23R||rs11209026||G > A||0.062||9.10e-14C||1.89 (1.56-2.27)D|
|2p15||chr2:62238413-62405459||rs4672495||A > C||0.330||3.20e-09C||1.18 (1.09-1.27)D|
|2p15||chr2:62256286-62420888||rs10865331||G > A||0.400||1.90e-19C||1.27 (1.18-1.37)D|
|2q11.2||chr2:101678428-102080305||IL1R2||rs2310173||C > A||0.450||4.80e-07C||1.18 (1.10-1.27)D|
|4q21.21||chr4:79783694-80069700||ANTXR2||rs4333130||A > G||0.360||9.30e-08C||1.22 (1.12-1.32)D|
|5q15||chr5:96638641-97038254||ERAP1||rs27037||C > A||0.290||8.20e-11C||1.23 (1.14-1.33)D|
|5q15||chr5:96647765-97039314||ERAP1||rs27434||G > A||0.230||5.30e-12C||1.19 (1.10-1.30)D|
|21q22.2||chr21:39081110-39111851||rs2242944||G > A||0.370||8.30e-20C||1.39 (1.28-1.49)D|
GDXHsS00012 meets the following criteria: